This purpose of this research is to study the secretion of catecholamines, epinephrine and norepinephrine, from the adrenal medulla, and to elucidate the mechanisms by which secretory stimuli, including acetylcholine and angiotensin II, regulate adrenal catecholamine secretion. Previous studies have shown that catecholamine secretion occurs by exocytosis, that Ca ions are required for this process, and that secretion is stimulated by acetylcholine and by angiotensin II. Recently, methods have been developed for the study of catecholamine secretion by isolated adrenal cells, in vitro. In the proposed research, catecholamine secretion by isolated chromaffin cells will be studied in more detail, in order to characterize this process more fully, and to correlate the metabolic effects of secretory stimuli on chromaffin cells with their effects on catecholamine synthesis and secretion. Catecholamine secretion by isolated pheochromocytoma cells will also be studied, and will be compared to the secretory process in normal chromaffin cells. In addition, catecholamine synthesis and secretion will be studied in normal and neoplastic chromaffin cells maintained in tissue culture. Finally, the osmotic behavior and permeability properties of isolated chromaffin granules will be studied, and the effects of ionophores on the release of catecholamines from these granules will be characterized.